Particles with designed different sized discrete pores

ABSTRACT

Polymeric porous particles have a continuous organic solid phase and at least two sets of discrete pores that are isolated from each other within the continuous phase and that have different average sizes. One set of discrete pores has a larger average size than another set of discrete pores by at least 50%. At least one set of discrete pores is free of detectably different marker materials. There porous particles can be prepared using evaporative limited coalescence techniques with especially chosen discrete pore stabilizing hydrocolloids to protect the pores during formation and to provide the different average sizes. The resulting porous particles can be incorporated into articles of various types and having various shapes.

RELATED APPLICATION

This application is a divisional of U.S. Ser. No. 13/749,748, filed Jan.25, 2013, recently allowed.

FIELD OF THE INVENTION

This invention relates to porous particles having at least two discretepores within a continuous polymer phase, and each set of discrete poreshave a different average size. This invention also relates to a methodfor making such porous particles in which the pores are designed to havedifferent average sizes, for example, bimodal or multimodal sizedistributions. This method can be used to design specific physicalproperties into the porous particles.

BACKGROUND OF THE INVENTION

Porous polymeric particles have been prepared and used for manydifferent purposes. For example, porous particles have been describedfor use in chromatographic columns, ion exchange and adsorption resins,drug delivery devices, cosmetic formulations, papers, and paints. Themethods for generating pores in polymeric particles are well known inthe field of polymer science. However, each particular porous particleoften requires unique methods for their manufacture. Some methods ofmanufacture produce large particles without any control of the pore sizewhile other manufacturing methods control the pore size withoutcontrolling the overall particle size.

Marker material can be included in porous particles so that theparticles can be detected for a specific purpose. For example, U.S.Patent Application Publications 2008/0176157 (Nair et al.) and2010/0021838 (Putnam et al.) and U.S. Pat. No. 7,754,409 (Nair et al.)describe porous particles and a method for their manufacture, whichporous particles are designed to be toner particles for use inelectrophotography. Such porous particles (“toners”) can be preparedusing a multiple emulsion process in combination with a suspensionprocess (such as “evaporative limited coalescence”, ELC) in areproducible manner and with a narrow particle size distribution.

Toner particles having a luminescent material that includes quantum dotsare described in EP 2,025,525 (Wosnick et al.) and can be used to formdetectable markings on substrates. These toner particles can alsoinclude colorants or other detectable components.

U.S. Pat. No. 7,887,984 (Nair et al.) describes porous toner particlescomprising a continuous binder polymer phase and a second phase of ahydrocolloid in discrete pores. These porous toner particles areprepared using limited coalescence techniques.

U.S. Pat. No. 8,110,628 (Nair et al.) describes the preparation ofporous particles having first and second discrete pores in which areincorporated detectably different marker materials. Such porousparticles are prepared using multiple water-in-oil emulsions and variousdiscrete pore stabilizing hydrocolloids.

While the noted methods and porous particles provide significantadvances in the art, there is a need for a way to prepare porousparticles that can be free of detectable markers, but which have sets ofpores having different averages sizes, for example as bimodal ormulti-modal size distribution.

Porous polymeric particles of controlled size are useful in diverseapplications such as physical spacers, gaseous absorbers, opticalbarriers and diffusers, permeable barriers, electrophotographic toners,lubricants, dessicants, and dispersive media. Porous polymeric particleshaving discrete pores of controlled size are likewise of technologicalimportance to these and other applications where the precise control ofparticle density, optical scatter, particle modulus, or elasticity orinternal porous surface area is advantageous. There is a need to find away to prepare such porous polymeric particles in a reproducible manner.

SUMMARY OF THE INVENTION

The present invention provides a porous particle comprising a polymerthat provides a continuous solid phase including an external particlesurface, and at least first and second discrete pores that are isolatedfrom each other and dispersed within the continuous phase, the first andsecond discrete pores having first and second average sizes,

wherein the second average size is greater than the first average sizeby at least 50%, and the first or second discrete pores are free ofdetectably different marker materials.

A multiple number of such porous particles can be provided as an aqueousslurry or suspensions, or in an aqueous formulation.

This invention also provides an article comprising a plurality of theporous particles of the present invention. Representative examples ofsuch articles are described below but the present invention is notlimited to those specifically mentioned.

The present invention provides a method for preparing a porous particleof the present invention, the method comprising:

-   -   providing a first water-in-oil emulsion comprising a first        discrete pore stabilizing hydrocolloid in a first aqueous phase        that is dispersed within a first oil phase containing a first        organic polymer or polymer precursor and a first organic        solvent,    -   providing a second water-in-oil emulsion comprising a second        discrete pore stabilizing hydrocolloid in a second aqueous phase        that is dispersed within a second oil phase containing a second        organic polymer or polymer precursor and a first organic        solvent,        -   wherein the first discrete pore stabilizing hydrocolloid in            the first aqueous phase has a different osmotic pressure            than the second discrete pore stabilizing hydrocolloid in            the second aqueous phase, by at least 0.4 psi,    -   combining the first and second water-in-oil emulsions to form a        third water-in-oil emulsion,    -   dispersing the third water-in-oil emulsion in a third aqueous        phase, and    -   removing the first and second organic solvents to form porous        particles,        -   each formed porous particle having the composition and            properties as described herein.

The present invention provides a number of advantages. For example, itprovides porous particles that can be designed to have different sizeddiscrete pores, for example in bimodal or even multi-modal sizedistributions.

The present invention enables the preparation of these advantageousporous particles using multiple water-in-oil emulsions. The porouspolymer particle size, size distribution, and pore size distribution canbe controlled by the amount and type of “porogen” used to create thepores, as described below. For example, the use of different porestabilizing hydrophilic colloids having different osmotic pressure inaqueous solutions enables the user to “design” porous particles withdesired pore size distributions.

The ability to control the distribution and size of multiple populationsof discrete pores according to the present invention can create uniquedesirable physical properties such optical scatter, solution imbibition,solute or solvent retention and release.

The properties of aggregated groups of particles or films of the porousparticles of this invention can also be favorable for technologicalapplication after subsequent processing steps such as compaction, fusingor sintering.

It is also possible to mix various ratios of the porous particles ofthis invention, having different porosities, which would subsequentlystratify under centrifugation to form columns of porous particles ofcontrolled and continuous porosity change to improve the function ofseparation columns.

Moreover, it is believed that if controlled ratios of the porousparticles were placed into a mold and fused, the resulting polymericarticles can have controlled optical scatter properties based upon theratio and quantity of the initial porous particles. The method of thepresent invention can be readily scaled up to large-scale manufacturing.This advantage provides a desirable opportunity for designing poroussolids of controlled density and light scattering in polymeric solidsfor three-dimensional printing applications.

The present invention also provides an opportunity to incorporate amarking material selectively into one of the types (sizes) of pores toimpart added technological advantage for controlled release, reactivity,or surface area applications of the marker materials.

DETAILED DESCRIPTION OF THE INVENTION Definitions

As used herein to define various components of the porous particles,phases, and emulsions described herein, unless otherwise indicated, thesingular forms “a,” “an,” and “the” are intended to include one or moreof the components (that is, including plurality referents).

Each term that is not explicitly defined in the present application isto be understood to have a meaning that is commonly accepted by thoseskilled in the art. If the construction of a term would render itmeaningless or essentially meaningless in its context, the term'sdefinition should be taken from a standard dictionary.

The use of numerical values in the various ranges specified herein,unless otherwise expressly indicated otherwise, are considered to beapproximations as though the minimum and maximum values within thestated ranges were both preceded by the word “about.” In this manner,slight variations above and below the stated ranges can be used toachieve substantially the same results as the values within the ranges.In addition, the disclosure of these ranges is intended as a continuousrange including every value between the minimum and maximum values.

Unless otherwise indicated, % solids or weight % are stated in referenceto the total dry weight of a specific formulation, emulsion, orsolution.

Unless otherwise indicated, the terms “polymer” and “resin” mean thesame thing, and include both homopolymers having the same recurring unitalong the organic backbone, as well as copolymers having two or moredifferent recurring units along the backbone. Such polymers or resinsinclude but are not limited to, materials prepared by eithercondensation or free radical polymerization.

The term “ethylenically unsaturated polymerizable monomer” refers to anorganic compound that has one or more ethylenically unsaturatedpolymerizable groups (such as vinyl groups) that can be polymerized toprovide an organic backbone chain of carbon atoms, and optionallyvarious side chains attached to the organic backbone. The polymerizedproduct of a particular ethylenically unsaturated polymerizable monomer,within the organic backbone, is called a “recurring unit”. The variousrecurring units in the polymers are generally distributed along thebackbone of a given polymer in a random fashion, although blocks ofcommon recurring units can also be present along the organic backbone.

Uses

The porous particles of this invention can have various uses includingbut not limited to use in, cosmetic formulations, pharmaceuticals,paints, inks, adhesives, hydrophobic coatings, clear or coloredelectrophotographic toners, dessicants, gaseous absorbers, lubricants,and dispersive media. The porous particles can also be included invarnishes (colored or colorless) and other coating compositions,polymeric films and fibers, and formed polymer, glass, and ceramicarticles including ceramic substrates, bottles, and bottle caps.

Useful articles in which the porous particles can be incorporatedinclude but are not limited to, use in optical diffuser devices, papers,fabrics, fibers, molded objects, optical lenses, matte particles,filters, column media in chromatographic and ion exchange columns, drugdelivery devices, and articles (or objects) that can be used forthree-dimensional printing operations.

The proliferation of three-dimensional printing and the creation ofthree-dimensional solids from molded plastics make the utility ofcreating designer polymeric particles of controlled porosity and porevolume with multiple pore types of controlled density, controlledoptical properties, or controlled barrier properties, of greattechnological importance. In addition, the porous particles of thepresent invention can be water, small molecule, salt, or gaseousabsorbers to impart added functionality to objects created from theporous particles.

Porous Particles

The porous particles are generally prepared, as described below, usingmultiple water-in-oil emulsions in combination with an aqueoussuspension process, such as in the ELC process. Two or more water-in-oilemulsions can be originally prepared and used to provide two or morediscrete pores (that is, two or more different sets of pores) in theporous particles, which discrete pores can have different average sizes(defined below).

The terms “porous particle” or “porous particles” are used herein,unless otherwise indicated, to refer to materials of the presentinvention. The porous particles comprise a continuous solid (polymer)phase having an external particle surface and discrete pores (at leastfirst and second different discrete types of pores as defined below)dispersed within the continuous solid phase.

In many embodiments, the continuous solid phase of the porous particleshas the same composition. That is, the continuous solid phase is uniformin composition including any additives that may be incorporated into thepolymeric phase. In addition, if mixtures of polymers are used in thecontinuous solid phase, those mixtures are dispersed uniformlythroughout.

The terms “detectably different” or “detectably distinct” refer todifferent marker materials (or different mixtures of marker materialsdescribed below) being detectable from each other using suitabledetection means. The porous particles of this invention can containdetectably different marker materials, such as those described in U.S.Pat. No. 8,110,628 (noted above), but only if at least one set ofdiscrete pores contains none of such detectably different markermaterials. This means that none of such marker materials is purposelyadded during manufacture so that at least one set of discrete pores arevoid of such marker materials (at least the first or second discretepores are free of detectably different marker materials). In mostembodiments, the porous particles of this invention contain nodetectably different marker materials in any of the first and seconddiscrete pores, and in still other embodiments, the porous particlescontain essentially no detectably different marker materials in anypores (first, second, or any additional discrete pores), meaning thatthe total amount of such detectably different marker materials in all ofthe pores of the each porous particle is less than 5 weight % or evenless than 1 weight %, based on the total porous particle dry weight.

When present in the some embodiments, the detectably detectable markermaterials include but are not limited to colorants (dyes and pigments),metallic pigments, fluorescing materials, radioisotopes, metal oxides,metal hydroxides, metal sulfides, metal oxyhydroxides, luminescingcompounds, bioactive materials, reactive chemicals, and enzymes, asdescribed in more detail in U.S. Pat. No. 8,110,628 (noted above), thedisclosure of which is incorporated herein by reference.

The term “porogen” refers to a pore forming agent used to make theporous particles. In this invention, a porogen can be the porestabilizing hydrocolloid that can be used to modulate the pore sizedistribution within the porous particles.

As used in this disclosure, the term “isolated from each other” refersto the different (distinct) pores of different sizes that are separatedfrom each other by some of the continuous solid phase.

The terms “first discrete pore” and “second discrete pore” refer todistinct sets of isolated pores in the porous particles. Each distinctset of pores includes a plurality of pores, each of which pores isisolated from others pores in the set of pores, and the pores of eachset of pores are isolated from all other pores of the other sets ofpores in the porous particle. The first set of pores has a first averagepore size and the second (or additional) set of pores has a second (oradditional) average pore size, which second average size is average thanthe first average pore size. The word “discrete” is also used to definedifferent droplets of the first and second aqueous phases when they aresuspended in the oil (solvent) phase (described below).

The porous particles include “micro,” “meso,” and “macro” pores, whichaccording to the International Union of Pure and Applied Chemistry, arethe classifications recommended for pores less than 2 nm, from 2 nm andup to and including 50 nm, and greater than 50 nm, respectively. Theporous particles can include closed pores of all sizes and shapes (poresentirely within the continuous solid phase). While there can be openpores on the surface of the porous particle, such open pores are notpredominant and most pores of each set of pores are generally totallyenclosed by the continuous solid phase.

The size of the porous particle, the formulation, the pore stabilizinghydrocolloid, and manufacturing conditions are the primary controllingfactors for pore size. The first discrete pores generally have a firstaverage size of at least 0.3 μm and up to and including 3 μm, or morelikely at least 0.5 μm and up to and including 2 μm.

The second discrete pores generally have a first average size of atleast 0.45 μm and up to and including 10 μm, or more likely at least0.75 μm and up to and including 8 μm.

The first and second discrete pores in the porous particles havedifferent average sizes wherein the second average size of the seconddiscrete pores is greater than the first average size of the firstdiscrete pores by at least 50%, or typically by at least 100%, and up toand including 2,000%.

In some embodiments, the porous particles can comprise additionaldiscrete pores (additional sets of pores) besides the first and seconddiscrete pores. For example, the porous particles can comprise at leastthird discrete pores that have an average size that is different fromboth of the first and second average sizes described herein. Forexample, if present, the third discrete pores can have an average sizethat is at least 0.5 μm and up to and including 5 μm, and the averagesize can be smaller or larger than either or both of the first andsecond average sizes. These additional sets of pores are generallyprovided using discrete pore stabilizing hydrocolloids or differentosmotic pressures other than those used to prepare the first and seconddiscrete pores, as described below.

For spherical porous particles, the average size is an “averagediameter.” For non-spherical porous particles, the average size refersto the “average largest dimension”. Pore size can be determined byanalyzing Scanning Electron Microscopy (SEM) images of fractured porousparticles using a commercial statistical analysis software package tostudy the distribution of the pores within the porous particles, or bymanually measuring the pore diameters or largest dimensions using thescale in the SEM images. For example, the “average” pore size for eachset of pores can be determined by calculating the average diameter orlargest dimension (cross-sectional image) of 20 measured pores.

In some embodiments, the first discrete pores are predominantly nearerthen external particle surface compared to the second discrete pores. Inother words, the smaller pores are predominantly close to the externalparticle surface compared to the larger discrete pores. As used herein,the term “predominant” means that a larger number fraction of pores ofone size is found in a “shell” area nearer the surface of the porousparticle than one would expect based on the total number fraction of thetwo or more types (sizes) of pores present in the porous particle.

The porous particles generally have a mode particle size of at least 2μm and up to and including 50 μm, or typically at least 4 μm and up toan including 40 μm, or even at least 4 μm and up to and including 20 μm,with this mode particle size being measured by automated image analysisand flow cytometry using any suitable equipment designed for thispurpose. The mode particle size represents the most frequently occurringdiameter for spherical porous particles and the most frequentlyoccurring largest dimension for the non-spherical porous particles in aparticle size distribution histogram.

In general, the porous particles have porosity of at least 10% and up toand including 80%, or more likely at least 20% and up to and including50%, or typically at least 20% and up to an including 40%, all based onthe total dry porous particle volume. Unless otherwise indicated,porosity can be measured by the Mercury Intrusion Porosimetry techniquethat uses mercury intrusion to isostatically crush the porous particlesat elevated pressures. The decrease in mercury level in the penetrometercapillary is then measured as a function of the pressure needed to crushthe closed internal voids in the porous particles. A good correlationhas been established between the mercury intrusion technique and anindependent method of measuring porosity by aerodynamic sizing. Mercuryintrusion was also used to measure the density of a variety of solid andpowder samples of known or measured density with excellent accuracy.Other details of the mercury intrusion technique are known in the art.

In many embodiments of this invention, the first and second discretepores can also comprise first and second discrete pore stabilizinghydrocolloids, respectively, which compounds are described below. Thefirst and second discrete pore stabilizing hydrocolloids can be the sameor different compounds as long as they have different osmotic pressuresin aqueous solutions, which differences in osmotic pressure are chosenin the method of making the porous particles as described below, andprovide the different average sizes of the first and second discretepores. These materials are incorporated within the respective poresduring the preparation of the porous particles as described below.

The porous particles of this invention can be spherical or non-sphericaldepending upon the desired use. The shape of porous particles can becharacterized by an “aspect ratio” that is defined as the ratio of thelargest perpendicular length to the longest length of the particle.These lengths can be determined for example by optical measurementsusing a commercial particle shape analyzer such as the Sysmex FPIA-3000(Malvern Instruments). For example, porous particles that are considered“spherical” for this invention can have an aspect ratio of at least 0.95and up to and including 1. For the non-spherical porous particles ofthis invention, the aspect ratio can be as low as 0.1 and up to andincluding 0.95, and in some embodiments, the aspect ratio can be 0.99and down to and including 0.4.

The porous particles comprise a continuous solid phase including anexternal particle surface. This continuous solid phase is generallycomposed of one or more organic polymers that are capable of beingdissolved in a suitable solvent (described below) that is immisciblewith water wherein the organic polymer itself is substantially insolublein water. Useful organic polymers include those derived from vinylmonomers such as styrene monomers and condensation monomers such asesters and mixtures thereof. Such organic polymers include but are notlimited to, homopolymers and copolymers such as polyesters, styrenicpolymers (for example polystyrene and polychlorostyrene), monoolefinpolymers (for example, polymers formed from one or more of ethylene,propylene, butylene, and isoprene), vinyl ester polymers (for example,polymer formed from one or more of vinyl acetate, vinyl propionate,vinyl benzoate, and vinyl butyrate), polymers formed from one or moreα-methylene aliphatic monocarboxylic acid esters (for example, polymersformed from one or more of methyl acrylate, ethyl acrylate, butylacrylate, dodecyl acrylate, octyl acrylate, phenyl acrylate, methylmethacrylate, ethyl methacrylate, butyl methacrylate, and dodecylmethacrylate), vinyl ether polymers (such as polymers formed from one ormore of vinyl methyl ether, vinyl ethyl ether, and vinyl butyl ether),and vinyl ketone polymers (for example, polymers formed from one or moreof vinyl methyl ketone, vinyl hexyl ketone, and vinyl isopropenylketone). Particularly useful organic polymers include polystyrenes(including polymers of styrene derivatives), polyesters, styrene/alkylacrylate copolymers, styrene/alkyl methacrylate copolymers,styrene/acrylonitrile copolymers, styrene/butadiene copolymers,styrene/maleic anhydride copolymers, polyethylene resins, andpolypropylene resins. Other useful organic polymers includepolyurethanes, urethane acrylic copolymers, epoxy resins, siliconeresins, polyamide resins, modified rosins, paraffins, and waxes. Stillother useful organic polymers are polyesters of aromatic or aliphaticdicarboxylic acids with one or more aliphatic diols, such as polyestersof isophthalic or terephthalic or fumaric acid with diols such asethylene glycol, cyclohexane dimethanol, and bisphenol adducts ofethylene or propylene oxides. The polyesters can be saturated orunsaturated.

In particularly useful embodiments, the continuous solid phase comprisesone or more polymers selected from the group consisting of a polyester,styrenic polymer, mono-olefin polymer, vinyl ester polymer, α-methylenealiphatic mono-carboxylic acid ester polymer, vinyl ether polymer, andvinyl ketone polymer.

It is advantageous to utilize organic polymers in the continuous solidphase that have a viscosity of at least 1 cps and up to and including100 cps when measured as a 20 weight % solution in ethyl acetate at 25°C.

The continuous solid phase can also be provided from polymer precursors(described below) that are reacted or polymerized during preparation ofthe porous particles to form the desired organic polymer(s). Inparticular, such polymer precursors include ethylenically unsaturatedpolymerizable monomers (or oligomers).

The porous particles can also include one or more release agents such aswaxes and lubricants. Examples of useful release agents are provided forexample in U.S. Patent Application Publication 2008/0176157 (Nair etal.) that is incorporated herein by reference. Such compounds can bepresent in an amount of at least 0.1 weight % and up to and including 20weight % based on the porous particle dry weight.

In addition, the porous particles can also include one or more chargecontrol agents (either negative or positive charge control agents).Examples of such compounds are also described in U.S. Patent ApplicationPublication 2008/0176157 (noted above). They can be present in an amountof at least 0.1 weight % and up to and including 5 weight %, based onthe porous particle dry weight.

Moreover, the porous particles can comprise a surface stabilizingmaterial, as small solid organic or inorganic particles, on the externalparticle surface of the porous particles. Useful surface stabilizingagents include but are not limited to, organic stabilizers such aspoly(vinyl pyrrolidone) and poly(vinyl alcohol), inorganic stabilizerssuch as clay particles, colloidal silica (for example LUDOX™ or NALCO™),or polymer latex particles as described in modified ELC processdescribed in U.S. Pat. No. 4,833,060 (Nair et al.), U.S. Pat. No.4,965,131 (Nair et al.), U.S. Pat. No. 2,934,530 (Ballast et al.), U.S.Pat. No. 3,615,972 (Morehouse et al.), U.S. Pat. No. 2,932,629 (Wiley),and U.S. Pat. No. 4,314,932 (Wakimoto et al.), the disclosures of whichare hereby incorporated by reference. Any combination of these surfacestabilizing agents can also be used. The amount of surface stabilizingmaterials in the porous particles can be up to and including 10 weight%, based on the total porous particle dry weight.

The porous particles or mixtures of porous particles can be provided aspowders, or as aqueous suspensions or slurries. Such aqueous suspensionsor slurries can also include surfactants or suspending agents to keepthe porous particles suspended.

The other compositional features of the porous particles are describedin the following description of the desired method for preparing theporous particles.

Articles with Porous Particles

The porous particles can be incorporated in a suitable manner intovarious articles designed as films, fabrics, fibers, molded objects,membranes, tubes, and three-dimension solids. The porous particles canbe incorporated within the article, on one or more of its surfaces orboth internally and on one or more surfaces.

In some embodiments, a metallic column can be filled with the porousparticles of this invention and the porous particles could then beheated to cause the particle surfaces to stick. The speed of migrationof liquids or gases though the resulting column of porous particleswould vary depending upon the size of the molecules and their ability tomove in the space between and within the porous particles.

In other embodiments, a layer of porous particles of this inventionhaving different pore sizes could be annealed using a suitable solventto form a thin film optical diffuser with designed scattering propertiesdepending upon the optical scattering properties of the designed porousparticles.

In yet other embodiments, a series of porous particles could be createdand added to a three-dimension molding printer. This printer could makethree-dimensional objects of differing density, or porosity or opticalscattering based upon the chosen ratio of porous particles and thedesigned different sizes of pores within the porous particles.

In still other embodiments, a water soluble aromatic agent could beadded into the smaller pores of the porous particles of this invention,which water soluble aromatic agent could be retained inside the porousparticles and later released into a specified environment at a ratecontrolled by the number and size of the smaller pores relative to thelarger pores in the porous particles.

Method of Preparing Porous Particles

The process for making the porous particles basically involves theformation of three or more water-in-oil emulsions and their coordinationcombining or dispersing.

A first stable water-in-oil emulsion is formed, comprising a firstaqueous phase and generally comprising a first discrete pore stabilizinghydrocolloid, which first aqueous phase is dispersed in a suitable firstoil (solvent) phase containing a first polymer or first polymerprecursor that eventually helps form a continuous solid phase, whichfirst polymer or polymer precursor is dissolved in one or more firstorganic solvents (described below). This first aqueous phase creates thefirst discrete pores in the porous particles having a designed firstaverage size because of the particular choice of first discrete porestabilizing hydrocolloid and osmotic pressure compared to the otherwater-in-oil emulsions.

A second stable water-in-oil emulsion is also formed to provide a secondaqueous phase generally comprising a second pore stabilizinghydrocolloid, which second aqueous phase is dispersed in a suitablesecond oil (solvent) phase containing a second polymer or second polymerprecursor that eventually helps form the continuous solid phase, whichsecond polymer or polymer precursor is dissolved in one or more secondorganic solvents (described below). This second aqueous phase createsthe second discrete pores in the porous particles having a designedsecond average size that is larger than the first average size of thefirst discrete pores. The second pore stabilizing hydrocolloid andaqueous phase osmotic pressure are also chosen so provide the differencebetween first and second average sizes.

The first and second discrete pore stabilizing hydrocolloids (describedbelow) can be the same or different chemicals, or the same or differentmixtures of chemicals or concentrations, as long as the aqueous phase ofthe first water-in-oil emulsion (with the first pore stabilizinghydrocolloid) has a different osmotic pressure than the aqueous phase ofthe second water-in-oil emulsion (with the second pore stabilizinghydrocolloid), by at least 0.4 psi, and typically by at least 0.4 psiand to and including 25 psi, or more likely a different osmotic pressureof at least 0.08 psi to and including 10 psi.

Suitably different osmotic pressures of the aqueous phases can beachieved in a number of ways, including but not limited to:

1) Embodiments in which the first and second discrete pore stabilizinghydrocolloids are present in the first and second aqueous phases,respectively, at different concentrations suitably to provide differentosmotic pressures of the aqueous phases. In such embodiments, the firstand second discrete pore stabilizing hydrocolloids can be the samechemical compounds (same chemical composition and molecular weight).Alternatively, the first and second discrete pore stabilizinghydrocolloids can be different chemical compounds (different chemicalcompositions or the same chemical composition with different molecularweights).

2) Embodiments in which the first and second discrete pore stabilizinghydrocolloids are present in the first and second aqueous phases at thesame concentration, and typically such discrete pore stabilizinghydrocolloids are different chemical compounds, or they are compoundsthat have the same chemical composition but different molecular weights.

3) Embodiments in which the first and second discrete pore stabilizinghydrocolloids are used in aqueous phases at different pH values suchthat the osmotic pressures are different in the first and second aqueousphases even when the pore stabilizing hydrocolloids are the samechemical compound and are present in the two aqueous phase at the sameconcentration.

4) Embodiments in which the first and second discrete pore stabilizinghydrocolloids can be held at different ionic strengths such that theosmotic pressures are different in the two aqueous phases of theemulsions even if the pore stabilizing hydrocolloids are the samechemical composition and are present at the same concentration.

5) Embodiments in which the first and second discrete pore stabilizinghydrocolloids have a combination of different pH, ionic strength,chemical composition, molecular weight, and counter ions such that theosmotic pressures are different in the two aqueous phases.

One can achieve a difference in osmotic pressure in an aqueous phase ofthe first or second water-in-oil emulsion either by increasing theconcentration of the discrete pore stabilizing hydrocolloid or byincreasing the charge on the discrete pore stabilizing hydrocolloid (thecounter-ions of the dissociated charges on the discrete pore stabilizinghydrocolloid increase its osmotic pressure). It can be advantageous tohave weak base or weak acid moieties in the discrete pore stabilizinghydrocolloids that allow for their osmotic pressures to be controlled bychanging the pH. Such discrete pore stabilizing hydrocolloids areconsidered “weakly dissociating hydrocolloids”. For these weaklydissociating hydrocolloids, the osmotic pressure can be increased bybuffering the pH to favor dissociation, or by simply adding a base (oracid) to change the pH of the aqueous phase to favor dissociation. Oneexample of such a weakly dissociating hydrocolloid is CMC that has a pHsensitive dissociation (the carboxylate is a weak acid moiety).

Suitable discrete pore stabilizing hydrocolloids for preparing all ofthe water-in-oil emulsions described herein include both naturallyoccurring and synthetic, water-soluble or water-swellable polymersselected from the group consisting of cellulose derivatives [such forexample, carboxymethyl cellulose (CMC) that is also referred to assodium carboxymethyl cellulose], gelatin (for example, alkali-treatedgelatin such as cattle bone or hide gelatin, or acid treated gelatinsuch as pigskin gelatin), gelatin derivatives (for example, acetylatedgelatin and phthalated gelatin), proteins and protein derivatives,hydrophilic synthetic polymers [such as poly(vinyl alcohol), poly(vinyllactams), acrylamide polymers, polyvinyl acetals, polymers of alkyl andsulfoalkyl acrylates and methacrylates, hydrolyzed polyvinyl acetates,polyamides, polyvinyl pyridine, and methacrylamide copolymers], watersoluble microgels, polyelectrolytes [such as a polystyrene sulfonate,poly(2-acrylamido-2-methylpropanesulfonate), and a polyphosphate], andmixtures of any of these classes of materials. Other syntheticpolyelectrolyte hydrocolloids such as polystyrene sulfonate (PSS),poly(2-acrylamido-2-methylpropanesulfonate) (PAMS), and polyphosphatesare also useful discrete pore stabilizing hydrocolloids.

For example, the first and second discrete pore stabilizinghydrocolloids can be selected from the group consisting of carboxymethylcellulose (CMC), a gelatin, a protein or protein derivative, ahydrophilic synthetic polymer, a water-soluble microgel, a polystyrenesulfonate, poly(2-acrylamido-2-methylpropanesulfonate), and apolyphosphate.

The first and second oil phases can comprise the same or differentorganic solvents (described below), or the same or different mixtures oforganic solvents. In most embodiments, the first and second oil phasescontain the same organic solvents. Further, the first and secondpolymers or first and second polymer precursors used in preparing thefirst and second oil phases can be the same or different compounds, ormixtures of compounds, but in most embodiments, they are the samepolymer compound or same polymer precursor that is used to prepare thedesired polymer compounds.

In order to stabilize the first and second water-in-oil emulsions sothat they can be held without ripening or coalescence, it is desiredthat the first and second discrete pore stabilizing hydrocolloids in thefirst and second aqueous phases have a higher osmotic pressure than thatof the first and second oil phases depending on the solubility of waterin the oil. This reduces the diffusion of water into the oil phases fromthe aqueous phases and thus the ripening caused by migration of waterbetween the water droplets. The discrete pore stabilizing hydrocolloidsare soluble in water, have no negative impact on multiple emulsificationprocesses, and have no negative impact on melt rheology of the resultingporous particles. It is important that the pore stabilizing hydrocolloidhave minimal solubility in the organic solvent so that it does notmigrate between into the organic phase, thus reducing the osmoticpressure of the aqueous phase.

The amount of the first and second discrete pore stabilizinghydrocolloids used to prepare the first and second water-in-oilemulsions (and any additional water-in-oil emulsions) will depend on theamount of porosity and size of discrete pores desired and the molecularweight and charge of the discrete pore stabilizing hydrocolloid that ischosen.

The first and second aqueous phases used in forming the first and secondaqueous water-in-oil emulsions can additionally contain, if desired,salts to buffer the emulsions and optionally to control the osmoticpressure of the aqueous phases. When CMC is used as a discrete porestabilizing hydrocolloid, for example, the osmotic pressure can beincreased by buffering using a pH 7 buffer. The first and secondwater-in-oil emulsions can also contain additional discrete pore formingagents such as ammonium carbonate.

The first and second organic polymers used in the first and secondwater-in-oil emulsions (or additional water-in-oil emulsions) to providethe continuous solid phase of the porous particles can be any type ofpolymer or resin or polymer precursor (described above) that is capableof being dissolved in a suitable solvent (described below) and that isimmiscible with or only slightly soluble in water (less than 10%solubility) wherein the organic polymer itself is substantiallyinsoluble in water.4

Any suitable organic solvent that will dissolve the organic polymer(s)or polymer precursors and that is also immiscible with or slightlysoluble in water (less than 10% solubility) can be used to prepare thefirst and second water-in-oil emulsions (or additional water-in-oilemulsions). Such organic solvents include but are not limited to, ethylacetate, propyl acetate, chloromethane, dichloromethane, vinyl chloride,trichloromethane, carbon tetrachloride, ethylene chloride,trichloroethane, toluene, xylene, cyclohexanone, 2-nitropropane,dimethyl carbonate, and mixtures of two or more of these solvents. Ethylacetate and propyl acetate are generally good solvents for many usefulpolymers while being sparingly soluble in water, and they are readilyremoved as described below by evaporation.

Optionally, the organic solvents that will dissolve the organic polymersand that is immiscible with water can be a mixture of two or morewater-immiscible solvents chosen from the list given above. For example,the oil phase can comprise a mixture of one or more of the above organicsolvents with a water-immiscible nonsolvent for the organic polymer suchas heptane, cyclohexane, and diethylether that is added in a proportionthat is insufficient to precipitate the organic polymer prior to dryingand isolation.

Alternatively, the one or more first and second oil phases (organicsolvents) can be replaced with one or more ethylenically unsaturatedpolymerizable monomers as polymer precursors and a polymerizationinitiator to form water-in-oil-in-water emulsions. The ethylenicallyunsaturated polymerizable monomers in the emulsified mixture can bepolymerized in the third water-in-oil emulsion (described below), forexample through the application of heat or radiation (for exampleactinic or IR radiation) after the third step (described above).Optional organic solvents (described above) can be present in smallamounts and have sufficient solubility in water that they can be removedby washing with water. This washing can occur simultaneously with afiltration process. The resulting suspension polymerized precursorporous particles can be isolated and dried as described earlier to yieldporous particles of this invention. In addition, either or both oilphases can contain both ethylenically unsaturated polymerizable monomersand organic polymers as described above. Useful ethylenicallyunsaturated polymerizable monomers and polymerization initiators wouldbe readily apparent to one skilled in the art.

Depending upon the ultimate use of the porous particles, the first andsecond water-in-oil emulsions can also include various additives,generally that are added to the organic polymer or polymer precursorprior to their dissolution in the organic solvent, during dissolution,or after the dissolution step itself. Such additives can include but arenot limited to, charge control agents, shape control agents,compatibilizers, wetting agents, surfactants, plasticizers, and releaseagents such as waxes and lubricants. Combinations of these materials canalso be used. At least one of the first and second aqueous phases caninclude a buffering salt examples of which are readily known in the art.

As noted above, some of the discrete pores can contain a detectablydifferent marker material as long as either of the first or seconddiscrete pores contains none of these detectably different markermaterials. This is achieved by including the detectably different markermaterials in the appropriate oil phase of the water-in-oil emulsion.Also, as noted above, in some embodiments, all of the discrete porescontain no detectably different marker materials and thus, none of thesematerials are purposely added to the first and second (and additional)water-in-oil emulsions.

For example, in some of the embodiments of the method, none of thefirst, second, and third water-in-oil emulsions contains a detectablydifferent marker material. In other embodiments of the method, the firstor second water-in-oil emulsion contains no detectably different markermaterial.

The first and second water-in-oil emulsions (and any additionalwater-in-oil emulsions) used to prepare the porous particles can beprepared by any known emulsifying technique and conditions using anytype of mixing and shearing equipment. Such equipment includes but isnot limited to, a batch mixer, planetary mixer, single or multiple screwextruder, dynamic or static mixer, colloid mill, high pressurehomogenizer, sonicator, or a combination thereof. While any high sheartype agitation device is useful, a particularly useful homogenizingdevice is the Microfluidizer® such as Model No. 110T produced byMicrofluidics Manufacturing operating at >5000 psi. In this device, thedroplets of the first and second aqueous phases can be dispersedseparately and reduced in size in the respective oil (organic) phases ina high flow agitation zone and, upon exiting this zone, the particlesize of the dispersed aqueous phases is reduced to uniform sizeddispersed droplets in each of the respective oil phases. The temperatureof the dispersing process can be modified to achieve the optimumviscosity for emulsification of the droplets and to minimize evaporationof the oil phases.

The first and second water-in-oil emulsions are combined to form a thirdwater-in-oil emulsion containing a mixture of the first and second oilphases and distinct droplets of the first and second aqueous phaseswithin those oil phases. These two populations of water-in-oil dropletsoriginating from the two emulsions can have measurably different orsimilar sizes. The blended emulsion droplet size distribution can bequantified either by direct optical microscopy with image analysis orusing a particle sizing techniques, such as Horiba low angle laser lightscattering or dynamic light scattering (Zen sizing). In embodimentswhere there is sufficient size difference between the droplets of thetwo emulsions, the blended emulsions show a distinct bimodaldistribution. This bimodal distribution may or may not be properlyseparated using light scattering methods, but is easily verified usingoptical image analysis methods. Even in certain embodiments in which thewater-in-oil droplets are too similar in size to allow discriminationbetween the emulsion droplet size directly, upon equilibration with athird water phase, evaporative limited coalescence, osmotic shock anddrying, the resultant pores of the porous particles can be of measurablydifferent sizes due to the amplification of the differences between theoriginal water-in-oil emulsion droplets sizes upon osmotic equilibrationwith the third (exterior) aqueous phase.

In some embodiments, a third oil phase (containing any of the organicsolvents from the list of organic solvents described above) containing athird organic polymer or polymer precursor (chosen from the list oforganic polymers described above) can be combined with the first andsecond water-in-oil emulsions. The third organic polymer can be the sameor different from the first and second organic polymers described above.The third oil phase containing the third organic polymer can be combinedin this manner in any suitable amount in relation to the first andsecond water-in-oil emulsions, for example, but not limited to, a weightratio of from 100:1 and to and including 1:100. The addition of thethird oil phase allows the manufacture to use stock solutions of thefirst and second water-in-oil emulsions and to modify them as desiredwithout having to make up fresh water-in-oil emulsions.

Thus, the method of this invention can further comprise:

-   -   providing an additional water-in-oil emulsion comprising a        discrete pore stabilizing hydrocolloid (different in some manner        from the first and second discrete pore stabilizing        hydrocolloids) in an additional aqueous phase that is dispersed        within an additional oil phase containing an additional organic        polymer or polymer precursor and an additional organic solvent,        and    -   combining the additional water-in-oil emulsion with the first        and second water-in-oil emulsions to form the third water-in-oil        emulsion.

The first and second water-in-oil emulsions (and any additionalwater-in-oil emulsions) can be combined in the third water-in-oilemulsion in any desirable weight ratio. For example, in someembodiments, the weight ratio of the first water-in-oil emulsion to thesecond oil-in-water emulsion can be at least 1000:1 and to and including0.01:1.

The third water-in-oil emulsion is then dispersed within a third aqueousphase that can contain a surface stabilizing material (described above)to form a water-in-oil-in-water emulsion containing droplets of thethird water-in-oil emulsion that contain the distinct droplets of thefirst and second aqueous phases. For example, the water-in-oil emulsioncan be dispersed within the third aqueous phase in the presence of acolloidal silica surface stabilizing material to form awater-in-oil-in-water emulsion containing an aqueous suspension of oildroplets of the third water-in-oil emulsion, wherein the oil dropletscontain discrete smaller droplets of the first and second aqueousphases.

The amount of surface stabilizing material (described above) used in themethod of this invention can be at least 0.1 weight % and up to andincluding 10 weight %, or typically at least 0.2 weight % and up to andincluding 5 weight %, based on the total weight of thewater-in-oil-in-water emulsion (third water-in-oil emulsion) anddepending upon the particle size of the surface stabilizing material(for example, colloidal or fumed silica particles) and the size of theoil droplets desired to be formed in the third water-in-oil emulsion.

The resulting water-in-oil-in-water emulsion is subjected to shear orextensional mixing or similar flow processes, for example through acapillary orifice device to reduce the first and second aqueous phasedroplet size to achieve narrow size distribution droplets through thelimited coalescence process. The pH of the third aqueous phase isgenerally at least 4 to and including 7 when colloidal silica is used asthe surface stabilizing material.

It can also be useful to add a shape control agent (described below) tothe third aqueous phase, or alternatively, to at least one of the firstand second oil phases.

The suspension of droplets of the first and second water-in-oilemulsions in the third aqueous phase results in droplets of organicpolymer(s) or polymer precursor dissolved in oil containing the firstand second aqueous phase as distinct finer droplets within the biggerorganic polymer droplets that upon drying produce first and seconddiscrete pores in the resultant porous particles containing the organicpolymer as a continuous solid phase.

When the water-in-oil-in-water emulsion is formed, shear or extensionalmixing or flow process can be controlled in order to minimize disruptionof the distinct droplets of the first and second aqueous phases in themixture of first and second oil phases. Droplet size reduction isachieved by homogenizing the third emulsion through a capillary orificedevice, or other suitable flow geometry. The shear field used to createthe droplets in the third water-in-oil emulsion can be created usingstandard shear geometries, such as an orifice plate or capillary.However, the flow field can also be generated using alternativegeometries, such as packed beds of beads, or stacks or screens thatimpart an additional extensional component to the flow. It is well knownin the literature that membrane-based emulsifiers can be used togenerate multiple emulsions. The techniques allow the droplet size to betailored across a wider range of sizes by adjusting the void volume ormesh size, and can be applied across a wide range of flow rates. Theback pressure suitable for producing acceptable porous particle size andsize distribution is at least 100 psi and up to and including 5000 psior typically at least 500 psi and up to and including 3000 psi. The flowrate is generally at least 1000 ml/min and up to and including 6000ml/min particularly when a capillary orifice device is used.

If desired, additional water can be added to the third aqueous phase ofthe water-in-oil-in-water emulsion to further control the average sizeof any or all of the sets of discrete pores by creating an additionalosmotic mismatch, for example of at least 0.4 psi, with either the firstor second aqueous phase. For example, the amount of dilution of thewater-in-oil-in-water emulsion can be at least 50% and up to andincluding 500%.

The first and second organic solvents of the oil phases are removed toproduce an aqueous suspension of uniform particles. Removal of theorganic solvents provides precursor porous particles that are thensubjected to isolation and drying techniques to provide the porousparticles. The details of this process depend upon the water solubilityand boiling points of the organic solvents in the oil phases relative tothe temperature of the drying process. Generally, however, organicsolvents can be removed by evaporation using removal apparatus such as arotary evaporator or a flash evaporator. The porous particles can thenbe isolated from the precursor porous particles after removing theorganic solvents by filtration or centrifugation, followed by drying forexample in an oven at 40° C. that also removes any water remaining inthe first and second discrete pores (and any additional discrete pores).Optionally, the porous particles can be treated with alkali to removeany silica surface stabilizing material.

The shape of the porous particles can be modified if desired. Shapecontrol agents can be incorporated into the first or second aqueousphases, in the first or second oil (organic) phase or in the thirdaqueous phase to modify the shape, aspect ratio, or morphology of theporous particles. The shape control agents can be added after or priorto forming the water-in-oil-in-water emulsion. In either case, theinterfacial tension at the oil and third water interface is modifiedbefore organic solvent is removed, resulting in a reduction insphericity of the porous particles. Some useful shape control agents arequaternary ammonium tetraphenylborate salts described in U.S. PatentApplication Publication 2007/0298346 (Ezenyilimba et al.), metal saltsdescribed in U.S. Patent Application Publication 2008/0145780 (Yang etal.), carnauba waxes described in U.S. Pat. No. 5,283,151 (Santilli),SOLSPERSE® hyperdispersants as described in U.S. Pat. No. 5,968,702(Ezenyilimba et al.), metal salts as described in U.S. Pat. No.7,655,375 (Yang et al.), and zinc organic complexes as described in U.S.Pat. No. 7,662,535 (Yang et al.). The disclosure of each of thesepublications is incorporated herein by reference. The more desirableshape control agents are polyethyloxazoline, fatty acid modifiedpolyesters such as EFKA® 6225 and EFKA® 6220 from Ciba BASF, andphosphate esters of alkoxylated phenols such as SynFac® 8337.

The following Examples are provided to illustrate the practice of thisinvention and are not meant to be limiting in any manner. In thefollowing Examples:

The polyester resin, Kao E, was obtained from Kao Specialties AmericasLLC, a part of Kao Corporation (Japan). Carboxy methylcellulose (Mw250K) was obtained from Acros Organics or from Ashland Aqualon asAqualon 9M31F. These were used interchangeably.

Carboxy methylcellulose, low viscosity (Mw 80,000) and Ludox™ colloidalsilica were obtained from Sigma-Aldrich Co.

Nalco™ 1060 colloidal silica was obtained from Nalco Chemical Company asa 50 weight % aqueous dispersion.

The (number) mean size of the particles was measured by fitting theperimeters of scanning electron micrograph (SEM) images and averagingthe results. A second method, the MS-3 Beckman Coulter Counter, was alsoused on select samples. The coulter counter measures the particle sizebased upon the conductivity contrast between the particle andsurrounding electrolyte media as the fluid containing the particlepasses through a small orifice. The Coulter Counter gives much betterstatistics measuring thousands of particles rather than the typical 5-10particles measured in an SEM image. However, the Coulter Counterelectrical signal needs calibration to a standard bead (typically solidpolystyrene) to determine the particle size. Because of the possibilityof low density porous particles with some pores open to the electrolyteat the surface changing the conductivity contrast compared to the solidbeads, we report primarily the SEM results which generally comparefavorably to the Coulter Counter results.

To further characterize the porosity and distribution of pore sizeswithin a given porous particle, representative SEMs were taken offractured porous particles and simple image analysis methods were usedto identify the pores within the porous particles and then to measurethe diameter of the pores. The ratio of the area of pores to the totalarea of the particle in the best flat region of a cross section was usedas a measure of percent porosity.

The cross section of a particle is a 2D planar slice through a 3Dspherical structure so that the measured circular “pores” are actuallyplanar slices through individual spherical pores. The measured size ofthese pores will appear smaller and more broadly distributed than thetrue diameter because most planar slices will not fall exactly throughthe center of the pores. We report the average of the maximum size poremeasured from several particles. For the bimodal porous particles wereport the average of the maximum size pore for both the large and smallpores measured from several particles. Clearly this method requiressufficient separation between the bimodal pore sizes to identify largeand small pores unambiguously.

Another method of measuring the size and shape of the porous particlesis to use a Sysmex FPIA-3000 automated particle shape and size analyzerfrom Malvern Instruments. In this method, samples are passed through asheath flow cell that transforms the particle suspension into narrow orflat flow, ensuring that the largest area of the particle is orientedtowards the camera and that all particles are in focus. The CCD cameracaptures 60 images every second and these are analyzed in real time.Numerical evaluation of particle shape is derived from measurement ofthe area of the particle. A number of shape factors are calculatedincluding circularity, aspect ratio, and circle equivalent diameter. Forthis instrument the reported size of the particles is the mode value ofthe distribution.

Unless otherwise indicated, the porous particle porosity was determinedusing Mercury Intrusion Porosimetry.

The porous polymer particles used in the Examples were made using thefollowing procedures:

Control 1: Porous Particles Prepared Using 5% 80K CMC without OrificeHomogenizer

An organic solvent (oil) phase was prepared using 85 g of a 20 weight %solution of Kao E in ethyl acetate. This oil phase was emulsified withan aqueous phase containing 26.25 g of a 3.24 weight % solution of 80kilodalton CMC using the Silverson Mixer followed by homogenization inthe Microfluidizer® at 8000 psi yielding a water-in-oil emulsion. A 61 galiquot of this emulsion was emulsified into a water phase consisting of150 g of a 200 mmolar citrate phosphate buffer at pH 4 and 7 g of Ludox™using the Silverson Mixer fitted with a General-Purpose DisintegratingHead for two minutes at 2000 RPM to form a water-in-oil-in-wateremulsion. The ethyl acetate was removed by evaporation using a HeidolphLaborata rotary evaporator at 40° C. under reduced pressure. Theresulting milky white porous particles were sieved through a 20 μmmetallic mesh and washed with base and distilled water and then dried inan oven. SEM analysis of these particles yielded a mean size of 17.0 μmand a broad size distribution with standard deviation of more than 4 μm.Upon fracture and further SEM analysis, it was determined that theparticles had an averaged particle porosity of 29% and a mean pore sizeof 0.74 μm. Analyzing the images and finding the maximum pore sizeconsistent with fitting all of the pores into a 3D (three dimensional)structure yielded an average (max) pore size of 1.0 μm.

Control 2: Porous Particles Using 2% 250K CMC with Orifice Homogenizerand Post Make at 1:1 Dilution

An organic phase (894.7 g) containing 20 weight % of Kao E in ethylacetate was emulsified with an aqueous phase prepared with 290.3 g of a2.00 weight % of 250K CMC using the Silverson Mixer followed byhomogenization in the Microfluidizer® at 9800 psi to give a water-in-oilemulsion. An 183 g aliquot of this water-in-oil emulsion was then addedto a third aqueous phase consisting of 373 g of a 200 mmolar citratephosphate buffer at pH 4 and 16.8 g of Nalco™ 1060 using the SilversonMixer fitted with a General-Purpose Disintegrating Head for two minutesat 2000 RPM, followed by homogenization in an orifice disperser at 1000psi to form a water-in-oil-in-water emulsion. The ethyl acetate wasevaporated using a Heidolph Laborata rotary evaporator at 40° C. underreduced pressure. The resulting suspension of porous particles wasfiltered through a glass flitted funnel and the porous particles werewashed with distilled water and then dried under ambient conditions. SEManalysis of these milky white porous particles yielded a mean size of6.00 μm and a narrow size distribution with standard deviation of 0.59μm. For comparison, these porous particles had a size of 6.17 μm asmeasured by the Coulter Counter. Upon fracture and SEM analysis, theaveraged particle porosity was determined to be 60%. This porosity istwice the porosity of the porous particles of Control 1, consistent withthe 1:1 post make dilution inflating the porosity of the porousparticles. A mean pore size of 1.1 μm was measured. Analyzing the imagesand finding the maximum pore size consistent with fitting all of thepores into a 3D structure yielded an average (max) pore size of 1.3 μm.

Invention Example 1 Porous Particles from Two Water-in-Oil EmulsionsBlended with Different Molecular Weight Hydrocolloids with 70% 80K CMCand 30% 250K CMC giving Bimodal Pore Sizes

Porous particle of this invention were prepared using a first organicphase (134.8 g) containing 20 weight % of Kao E in ethyl acetate wasemulsified with the first aqueous phase prepared with 41.75 g of a 1.94weight % of 80K CMC using the Silverson Mixer followed by homogenizationin the Microfluidizer® at 9800 psi to give a first water-in-oilemulsion. A second water-in-oil emulsion was prepared with the secondorganic phase having 134.8 g of an 20.0 weight % of Kao E in ethylacetate, and the second aqueous phase containing 41.75 g of a 1.94weight % solution of 250K CMC in the same manner as the firstwater-in-oil emulsion. A 70 g aliquot of the first water-in-oil emulsionand a 30 g aliquot of the second water-in-oil emulsion were then blendedwith gentle mixing. Samples of this mixed first and second water-in-oilemulsion blend were viewed under optical microscopy and measured withHoriba light scattering. A 100 g aliquot of the mixture of first andsecond water-in-oil emulsions was then added to a third aqueous phaseconsisting of 159.7 g of a 200 mmolar citrate phosphate buffer at pH 4and 7 g of Nalco™ 1060 using the Silverson Mixer fitted with aGeneral-Purpose Disintegrating Head for two minutes at 2000 RPM,followed by homogenization in an orifice disperser at 1000 psi to form awater-in-oil-in-water emulsion. The ethyl acetate was evaporated using aHeidolph Laborata rotary evaporator at 40° C. under reduced pressure.The resulting suspension of porous particles was filtered through aglass fritted funnel and the polymeric particles were washed withdistilled water and then dried under ambient conditions. The resultingpolymeric porous particles had a mean size of 6.0 μm. The milky whiteparticles upon fracture and SEM image analysis had 23.4% porosity withtwo distinct populations of different sized pores. There were 80% smallpores of (max) size 0.83 μm and 20% large pores of (max) size 1.7 μm.This fraction reasonably reflects the expected 70/30 input fraction ofeach emulsion. The first emulsion with 80K CMC yields smaller pores asexpected reflecting the lower initial osmotic pressure of the lowermolecular weight CMC. The images show clearly that these are bimodalporous particles.

Invention Example 2 Porous Particles from Two Water-in-Oil EmulsionsBlended using Different Molecular Weight Hydrocolloids with 30% 80K CMCand 70% 250K CMC Giving Bimodal Pore Sizes

Porous particles of this invention were prepared as described inInvention Example 1 except that a 30 g aliquot of the first water-in-oilemulsion (with 1.94% 80K CMG) was added to a 70 g aliquot of the secondwater-in oil-emulsion (with 1.94% 250K CMC) with gentle mixing. Thismixture of first and second water-in-oil emulsions was then added to athird aqueous phase containing 159.7 g of the citrate phosphate bufferand 7 g of Nalco™ 1060. The homogenization, solvent evaporation, anddrying of the porous particles were carried out as described inInvention Example 1. The resulting porous particles, upon fracture andSEM image analysis, had a mean size of 6.3 μm and a porosity of 27.5%.The milky white porous particles had two separate populations ofdiscrete pores. The SEM image cross section had 35% small pores ofaveraged (max) size 0.42 μm and 65% large pores of averaged (max) size1.8 μm. This fraction reasonably reflected the expected 30/70 inputfraction of each emulsion in the water-in-oil-in-water emulsion. Thesecond emulsion with 250K CMC yielded larger pores as expectedreflecting the higher initial osmotic pressure of the higher molecularweight CMC.

Invention Example 3 Porous Particles from Two Water-in-Oil EmulsionsBlended Using Different Molecular Weight Hydrocolloids with 70% 80K CMCand 30% 250K CMC Giving Bimodal Pore Sizes with 1:1 Post Make Dilution

Porous particles of this invention were prepared as described inInvention Example 1 except that after the addition of the third waterphase and homogenization to form the water-in-oil-water emulsion, a 20 galiquot of the water-in-oil-water emulsion was diluted with 20 g of purewater. This 1:1 diluted water-in-oil-in-water emulsion was thensubjected to solvent evaporation, and drying of the porous particles asdescribed in Invention Example 1. The resulting porous particles uponfracture and SEM image analysis had a mean size of 6.4 μm and a porosityof 40.7%. The milky white porous particles had primarily separatepopulations of discrete pores. The SEM image cross section had 70% smallpores of averaged (max) size 0.57 μm and 30% large pores of averaged(max) size 2.32 μm. This fraction of pores matched excellently the 70/30fraction of the two emulsions used. The porosity was notably larger thanin Invention Example 1 due to the dilution step. In some porousparticles, the dilution step caused the largest pores to coalesce toform very large central pores surrounded by smaller pores around theperiphery of the particle (near the outer surface).

Invention Example 4 Porous Particles from Two Water-in-Oil EmulsionsBlended Using Different Molecular Weight Hydrocolloids with 30% 80K CMCplus 70% 250K CMC giving Bimodal Pore Sizes with 1:1 Post Make Dilution

Porous particles of this invention were prepared as described inInvention Example 2 except that after addition of the third water phaseand homogenization to form the water-in-oil-in-water emulsion, a 20 galiquot of this emulsion was diluted with 20 g of pure water. This 1:1diluted water-in-oil-in-water mixture was then subject to solventevaporation, and the porous particles were dried as described inInvention Example 1. The resulting porous particles upon fracture andSEM image analysis had a mean size of 7.0 μm and a porosity of 49.5%.The milky white porous particles had two separate populations of poreswith 39% small pores of average (max) size of 0.43 μm and 61% largepores of average (max) size 1.96 μm. This fraction reasonably reflectsthe expected input fraction 30/70 of each water-in-oil emulsion. Thesecond water-in-oil emulsion with 250K CMC again yielded larger pores asexpected reflecting the higher initial osmotic pressure of the highermolecular weight CMC. The porosity of the porous particles was notablylarger than in those prepared in Invention Example 2 due to the waterdilution step.

The invention has been described in detail with particular reference tocertain preferred embodiments thereof, but it will be understood thatvariations and modifications can be effected within the spirit and scopeof the invention.

1. An article comprising a porous particle that comprises one or moreorganic polymers that provide a continuous solid phase including anexternal particle surface, and at least first and second discrete closedpores that are isolated from each other and dispersed within thecontinuous phase, the first and second discrete closed pores havingfirst and second average sizes, wherein: the second average size isgreater than the first average size by at least 50%, the first or secondclosed discrete pores are free of detectably different marker materials,the porous particle has a mode particle size of at least 2 μm and up toand including 50 μm, and the first and second discrete closed porescomprise first and second discrete pore stabilizing hydrocolloids,respectively, which provide different osmotic pressures of at least 0.4psi.
 2. The article of claim 1 comprising a plurality of the porousparticles that are adhered to one another through an annealing process,or by chemical attachment.
 3. The article of claim 2 that is a moldedthree dimensional object or film with a designed variation in the indexof refraction and density achieved provided by the plurality of theporous particles.
 4. The article of claim 1, wherein the porous particlecomprises a marker material present within only the first discreteclosed pores or the second discrete closed sized pores.
 5. The articleof claim 1, wherein the second average size of the second discreteclosed pores is greater than the first average size of the firstdiscrete closed pores by at least 100%.
 6. The article of claim 1,wherein the first discrete closed pores are predominantly nearer theexternal particle surface of the porous particle compared to the seconddiscrete closed pores.
 7. The article of claim 1, wherein the first andsecond discrete pore stabilizing hydrocolloids are independentlyselected from the group consisting of carboxymethyl cellulose (CMC), agelatin or gelatin derivative, a protein or protein derivative, ahydrophilic synthetic polymer, a water-soluble microgel, a polystyrenesulfonate, poly(2-acrylamido-2-methylpropanesulfonate), and apolyphosphate.
 8. The article of claim 1, wherein the first discreteclosed pores have a first average size of at least 0.3 μm and to andincluding 3 μm, and the second discrete closed pores have a secondaverage size of at least 0.45 μm and to and including 10 μm.
 9. Thearticle of claim 1, wherein there are no detectably different markermaterials in the first and second discrete closed pores of the porousparticle.
 10. The article of claim 1, wherein there are no detectablydifferent marker materials in any of the first and second discreteclosed pores of the porous particle.
 11. The article of claim 1, whereinthe porous particle has a porosity of at least 20% and up to andincluding 50% based on total porous particle volume.
 12. A method forpreparing a porous particle, comprising: providing a first water-in-oilemulsion comprising a first discrete pore stabilizing hydrocolloid in afirst aqueous phase that is dispersed within a first oil phasecontaining a first organic polymer or polymer precursor and a firstorganic solvent, providing a second water-in-oil emulsion comprising asecond discrete pore stabilizing hydrocolloid in a second aqueous phasethat is dispersed within a second oil phase containing a second organicpolymer or polymer precursor and a second organic solvent, wherein thefirst discrete pore stabilizing hydrocolloid in the first aqueous phasehas a different osmotic pressure than the second discrete porestabilizing hydrocolloid in the second aqueous phase, by at least 0.4psi, combining the first and second water-in-oil emulsions to form athird water-in-oil emulsion, dispersing the third water-in-oil emulsionin a third aqueous phase, and removing the first and second organicsolvents to form porous particles, each formed porous particlecomprising the first and second organic polymers that provide acontinuous organic solid phase including an external particle surface,and at least first and second discrete closed pores that are isolatedfrom each other and dispersed within the continuous organic solid phase,the first and second discrete closed pores having first and secondaverage sizes, respectively, and comprising the first and seconddiscrete pore stabilizing hydrocolloids, respectively, wherein thesecond average size is greater than the first average size by at least50%, and the first or second discrete closed pores are free ofdetectably different marker materials.
 13. The method of claim 12,wherein the first and second discrete pore stabilizing hydrocolloids inthe first and second aqueous phases, respectively, have differentosmotic pressures of at least 0.4 psi and to and including 25 psi. 14.The method of claim 12, wherein the first and second discrete porestabilizing hydrocolloids are present in the first and second aqueousphases, respectively, at different concentrations.
 15. The method ofclaim 12, wherein the first and second discrete pore stabilizinghydrocolloids are the same chemical compounds.
 16. The method of claim12, wherein the first and second discrete pore stabilizing hydrocolloidsare different chemical compounds.
 17. The method of claim 12, whereinthe first and second discrete pore stabilizing hydrocolloids are presentin the first and second aqueous phases at the same concentration. 18.The method of claim 12, further comprising adding water to the thirdaqueous phase after dispersing the third water-in-oil emulsion in thethird aqueous phase.
 19. The method of claim 12, comprising adding waterto the third aqueous phase after dispersing the third water-in-oilemulsion in the third aqueous phase in an amount to provide an osmoticmismatch of at least 0.4 psi with either the first or the second aqueousphase.
 20. The method of claim 12, further comprising: providing anadditional water-in-oil emulsion comprising a discrete pore stabilizinghydrocolloid in an additional aqueous phase that is dispersed within anadditional oil phase containing an additional organic polymer or polymerprecursor and an additional organic solvent, and combining theadditional water-in-oil emulsion with the first and second water-in-oilemulsions to form the third water-in-oil emulsion.